4-(甲氧基噻吩基)-3-(取代苯甲酰基)-吡咯类化合物的合成与抗肿瘤活性研究

Synthesis and Anti-tumor Activity of 4-(Methoxyl thienyl)-3-(substituted benzoyl)pyrroles

分别以2-甲氧基噻吩、3-甲氧基噻吩、3,4-二溴噻吩和取代苯乙酮为原料,经过溴甲氧基取代反应、VilsmeierHack反应、羟醛缩合和Van Leusen吡咯合成法,设计并合成了33个未见文献报道的4-取代噻吩基吡咯类化合物.其结构均经~1H NMR,^(13)C NMR及HRMS确认,同时采用噻唑蓝(MTT)法测试了目标化合物对CHO、HCT-116、MGC80-3、SGC-7901以及HUVEC细胞增殖抑制活性.结果显示,部分化合对MGC80-3细胞有较强(IC_(50)≤20μml/L)或中等(20μmol/L<IC_(50)≤50μmol/L)增殖抑制作用,其中[4-(3,4-二甲氧基噻吩-2-基)-1H-吡咯-3-基](4-苯基苯基)甲酮(4a-2)和[4-(3,4-二甲氧基噻吩-2-基)-1H-吡咯-3-基](3-溴苯基)甲酮(4a-7)的IC_(50)值分别为8.6和8.5μmol/L;化合物4a-7对HCT-116细胞有中等抑制活性;化合物4a-2和4a-7对SGC-7901细胞有中等增殖抑制活性;并且几乎所有化合物对正常人体细胞HUVEC无明显抑制作用.

33 novel 4-substituted thienyl pyrrole compounds were synthesized via replacement, Vilsmeier-Hack, aldol con- densation and Van Leusen pyrrole reaction using 2-methoxythiophen, 3-methoxythiophene, 3,4-dibromothiophene and substi- tuted acetophenone as raw materials. The structures of all target compounds were characterized by 1H NMR, 13C NMR and HRMS, meanwhile the cell proliferation inhibition efficacy was estimated against CHO, HCT-116, MGC80-3, SGC-7901 and HUVEC cell lines. The results revealed that some target compounds exhibited strong （IC50〈20 pmol/L） or moderate （20 p, mol/L〈ICs0〈50 p, mol/L） proliferation inhibition efficacy against tumor cells, meanwhile no significant inhibition activity on HUVEC, which indicated that these compounds had high selectivity. Herein, some compounds showed strong or moderate inhibition efficacy against MGCS0-3. The ICs0 values of [4-（3,4-dimethoxythiophen-2-yl）-lH-pyrrol-3-yl]（4-phenylphenyl）- methanone （4a-2） and [4-（3,4-dimethoxythiophen-2-yl）-lH-pyrrol-3-yl]（3-bromophenyl）methanone （4a-7）, were 8.6 and 8.5 gmol/L against MGC80-3, respectively, and the IC50 value of 4a-7 was 20.0 μmol/L against HCT-116. Both compounds 4a-2 and 4a-7 exhibited moderate inhibition efficacy against SGC-7901.